自发性和治疗相关的乙型肝炎抗原缺失的耐久性。

StephenW

Clin Gastroenterol Hepatol. 2019 Jul 16. pii: S1542-3565(19)30751-7. doi: 10.1016/j.cgh.2019.07.018. [Epub ahead of print]
Durability of Spontaneous and Treatment-related Loss of Hepatitis B s Antigen.
Alawad AS1, Auh S2, Suarez D1, Ghany MG3.
Author information

1
    Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases.
2
    Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
3
    Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases. Electronic address: [email protected].

Abstract
BACKGROUND & AIMS:

Clearance of hepatitis B surface antigen (HBsAg) from serum is the most desirable endpoint and a proposed definition of functional cure for hepatitis B virus (HBV) infection. However, little is known about the long-term durability of HBsAg loss, and there is controversy over whether the development of antibodies against HBsAg (anti-HBs) is required for maintenance. We aimed to assess the durability of spontaneous or treatment-related (interferon or nucleos(t)ide analogue [NA]) loss of HBsAg.
METHODS:

We performed a retrospective study of patients with chronic HBV infection followed at the National Institutes of Health from February 1980 through November 2017. We identified those with HBsAg loss, confirmed on 2 visits at least 24 weeks apart. Patients with HCV, HDV, HIV, or HTLV-1 co-infection or HBsAg loss after liver transplantation were excluded. Patients were assigned to the following groups: spontaneous clearance (cleared HBsAg without ever receiving treatment or those who received treatment with a NA or interferon and discontinued therapy more than 5 years before HBsAg loss), interferon-treated (cleared HBsAg either during treatment or within 5 years after stopping interferon), and NA-treated (cleared HBsAg either during treatment or within 5 years after stopping NA).
RESULTS:

Among the 787 HBsAg-positive patients, 89 achieved HBsAg loss; 65/89 had confirmed HBsAg loss, which was spontaneous in 19 of the patients (29%), after interferon in 22 (34%), and after NA in 24 (37%). Of the 65 patients with confirmed loss of HBsAg, 62 patients (95%) remained HBsAg negative after a mean time of 9.6 years from first negative HBsAg test result. HBsAg sero-reversion occurred in 3 of the 46 treated patients (7%) (1 interferon and 2 NA), 1 of whom was positive for anti-HBs. At time of HBsAg loss, 33/65 (51%) were anti-HBs positive. At the last follow-up evaluation, anti-HBs was detectable in 50 of the 62 patients (81%) assessed. The rate of development of anti-HBs was proportionally higher among interferon-treated patients (19/21, 90%) than NA-treated patients (17/22, 77%) or patients with spontaneous loss of HBsAg (14/19, 74%).
CONCLUSIONS:

In a retrospective study of 787 HBsAg-positive patients, loss of HBsAg (either spontaneous or after treatment) was confirmed in 8% and was durable. Seroconversion to anti-HBs increased over time and appeared to be more frequent after interferon treatment. HBsAg loss is therefore a robust endpoint for functional cure.

Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS:

CHB; Outcome; Seroconversion; Vaccination

PMID:
    31323381
DOI:
    10.1016/j.cgh.2019.07.018

StephenW

Clin Gastroenterol Hepatol。 2019年7月16日.pii：S1542-3565（19）30751-7。 doi：10.1016 / j.cgh.2019.07.018。 [印刷前的电子版]
自发性和治疗相关的乙型肝炎抗原缺失的耐久性。
Alawad AS1，Auh S2，Suarez D1，Ghany MG3。
作者信息

1
    国家糖尿病与消化和肾脏疾病研究所肝病科。
2
    马里兰州贝塞斯达国立卫生研究院国家糖尿病与消化和肾脏疾病研究所所长办公室。
3
    国家糖尿病与消化和肾脏疾病研究所肝病科。电子地址：[email protected]。

抽象
背景与目的：

从血清中清除乙型肝炎表面抗原（HBsAg）是最理想的终点，并提出了乙型肝炎病毒（HBV）感染功能性治疗的定义。然而，关于HBsAg丢失的长期耐久性知之甚少，并且关于是否需要开发针对HBsAg（抗-HBs）的抗体进行维持存在争议。我们的目的是评估自发性或治疗相关（干扰素或核苷（酸）类似物[NA]）HBsAg丢失的持久性。
方法：

我们对1980年2月至2017年11月在美国国立卫生研究院进行的慢性HBV感染患者进行了一项回顾性研究。我们确定了HBsAg丢失的患者，至少间隔24周确诊2次。排除肝移植后HCV，HDV，HIV或HTLV-1共感染或HBsAg消失的患者。患者被分配到以下组：自发清除（未接受治疗的HBsAg清除或接受NA或干扰素治疗且HBsAg丢失前5年以上停止治疗的患者），干扰素治疗（治疗期间或治疗期间清除HBsAg）停止干扰素后5年）和NA治疗（治疗期间或停止NA后5年内清除HBsAg）。
结果：

在787例HBsAg阳性患者中，89例HBsAg消失; 65/89确认HBsAg丢失，其中19例患者（29％）自发性，22例干扰素（34％）和24例（37％）NA患者自发消退。在确诊的HBsAg消失的65名患者中，62名患者（95％）在首次HBsAg阴性检测结果的平均时间为9.6年后仍然为HBsAg阴性。 46例接受治疗的患者中有3例（7％）（1例干扰素和2例NA）发生HBsAg血清转换，其中1例抗-HBs阳性。在HBsAg丧失时，33/65（51％）为抗HBs阳性。在最后一次随访评估中，62例患者中有50例（81％）可检测到抗-HBs。干扰素治疗患者（19 / 21,90％）的抗-HBs发生率在比NA治疗患者（17 / 22,77％）或HBsAg自发丧失患者（14 / 19,74）中的比例更高。 ％）。
结论：

在一项对787例HBsAg阳性患者的回顾性研究中，HBsAg（自发性或治疗后）的丢失率确认为8％且持久。随着时间的推移，抗-HBs的血清转换增加，并且在干扰素治疗后似乎更频繁。因此，HBsAg损失是功能性治愈的有力终点。

版权所有©2019 AGA Institute。由Elsevier Inc.出版。保留所有权利。
关键词：

CHB;结果;血清转化;疫苗接种

结论：
    31323381
DOI：
    10.1016 / j.cgh.2019.07.018